title: Clinical profiles of Parkinson's disease associated with common leucine-rich repeat kinase 2 and glucocerebrosidase genetic variants in Chinese individuals.
abstract: Clinical profiles of Parkinson's disease (PD) related to LRRK2 (LRRK2-PD), and GBA (GBA-PD) genes have not been reported in Chinese individuals. In this study, we have investigated motor and non-motor aspects in 1638 Chinese PD patients who carried LRRK2 G2385R or R1628P (LRRK2-PD, n = 223), GBA L444P variant (GBA-PD, n = 49), or none of the variants (idiopathic PD [IPD], n = 1366). As a result, age at onset and motor and non-motor features of LRRK2-PD patients were similar to IPD patients except for milder non-motor symptoms. In contrast, GBA-PD patients had a significantly younger age at onset and higher Unified Parkinson's Disease Rating Scale scores than LRRK2-PD and IPD patients. In addition, postural instability and gait disorders, motor complications, cognitive decline, hallucination, sexual dysfunction, and constipation were more frequent in GBA-PD than in LRRK2-PD and IPD patients, and GBA-PD patients had a worse performance for social functioning and role-emotional scores. Our study represents the first large-scale clinical study of LRRK2-PD and GBA-PD in ethnic Chinese individuals. The data suggest that both LRRK2-PD and GBA-PD are similar to IPD, except for an earlier age at onset and relatively more common non-motor symptoms in GBA-PD patients. These findings strengthen our understanding of the clinical heterogeneity of PD, and may have implications for molecular classification of the disease.
authors.affiliation: Department of Neurobiology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Department of Neurology, Beijing Institute of Geriatrics, Xuanwu Hospital of Capital Medical University, Beijing, China; Key Laboratory on Neurodegenerative Disease of Ministry of Education and Key Laboratory on Parkinson's Disease of Beijing, Beijing, China; Department of Neurology, The Affiliated Sanming First Hospital of Fujian Medical University, Sanming, Fujian, China.
authors.forename: Chaodong
authors.initials: C
authors.lastname: Wang
authors.forename: Yanning
authors.initials: Y
authors.lastname: Cai
authors.forename: Zhuqin
authors.initials: Z
authors.lastname: Gu
authors.forename: Jinghong
authors.initials: J
authors.lastname: Ma
authors.forename: Zheng
authors.initials: Z
authors.lastname: Zheng
authors.forename: Bei-Sha
authors.initials: BS
authors.lastname: Tang
authors.forename: Yanming
authors.initials: Y
authors.lastname: Xu
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Zhou
authors.forename: Tao
authors.initials: T
authors.lastname: Feng
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Sheng-Di
authors.initials: SD
authors.lastname: Chen
authors.forename: Piu
authors.initials: P
authors.lastname: Chan
mesh_terms: D017668:Age of Onset; D000368:Aged; D044466:Asian People; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics*; D003071:Cognition; D003248:Constipation; D004644:Emotions; D005260:Female; D005684:Gait; D005962:Glucosylceramidase / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009043:Motor Activity; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000503:physiopathology / Q000523:psychology; D011187:Posture; D012735:Sexual Dysfunction, Physiological; D012919:Social Behavior
chemical_list: D015816:Cell Adhesion Molecules, Neuronal; C113373:LRRN2 protein, human; D005962:Glucosylceramidase
keywords: Clinical profiles; GBA; Genetic variant; LRRK2; Parkinson's disease